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Process for the preparation (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-amine di-HCl

IP.com Disclosure Number: IPCOM000240169D
Publication Date: 2015-Jan-08
Document File: 2 page(s) / 215K

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The IP.com Prior Art Database

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Process for the preparation (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H- pyrazolo [3,4-d]pyrimidin-4-amine di-HCl


(R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-amine (referred to herein as Compound I) was prepared by the following process:

a) Obtaining an activated form of tert-butyl (S)-3-hydroxypiperidine-1- carboxylate (i.e., mesylate/tosylate/nosylate/Chloride/ bromide/iodide) starting from tert-butyl (S)-3-hydroxypiperidine-1-carboxylate*;

b) Reacting the activated form of tert-butyl (S)-3-hydroxypiperidine-1- carboxylate with 3-(4- phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine in the presence of a base; and, optionally, isolating the obtained compound; and

c) Removing the Boc protecting group to obtain Compound I a salt thereof. The removal of the protecting group was done in the presence of an acid. The acid can be added in amount suitable for forming the corresponding acid addition salt.

Compound I was prepared as described above and was precipitated as di hydrochloride salt, having optical purity higher than 99.9%.


*The starting material tert-butyl (R)-3-hydroxypiperidine-1-carboxylate* is commercially available (ee > 99.7%).

Compound I or a salt thereof can be further used to prepare R)-1-(3-(4-amino-3-(4- phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (referred to as Compound A), using the following process, for example:


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OPh

NH

OPh N

OPh N

N

N

N

N N N

N N N

N N N

X

O

O

X=l...